In this renewal application, we propose to continue our investigation of the clinical immunobiology of immunodeficiency and cancer with four major objectives: (1) to define the various types of primary immunodeficiency in terms of underlying defects of cells of the T cell and B cell lineage, thymus function, phagocytic cells, and complement; (2) to dissect the secondary immunodeficiency associated with solid tumors, lymphomas, leukemias, and non-neoplastic disorders; (3) to characterize cancer cells immunologically, in terms of lymphocyte differentiation antigens, cell surface antigens not related to known differentiation antigens, shed antigens circulating as immune complexes, and other circulating markers; and (4) to develop more effective immunological approaches to the treatment of immunodeficiency and cancer. The thrust of our proposal is to develop, through better understanding of underlying mechanisms, more effective therapy. The basis of our operation is a close integration of two essential strengths of our center - a large population of patients with cancer and immunodeficiency, and a strong research program in immunobiology. The program project outlined here represents an effective catalyst.